The Arginine Methyltransferase PRMT6 Regulates DNA Methylation and Contributes to Global DNA Hypomethylation in Cancer
Year: 2017
Type: article
Abstract: DNA methylation plays crucial roles in chromatin structure and gene expression. Aberrant DNA methylation patterns, including global hypomethylation and regional hypermethylation, are associated with cancer and implicated in oncogenic events. How DNA methylation is regulated in developmental and cellular processes and dysregulated in cancer is poorly understood. Here, we show that PRMT6, a protein arginine methyltransferase responsible for asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a), negatively regulates DNA methylation and that PRMT6 upregulation contributes to global DNA hypomethylation in cancer. Mechanistically, PRMT6 overexpression impairs chromatin association of UHRF1, an accessory factor of DNMT1, resulting in passive DNA demethylation. The effect is likely due to elevated H3R2me2a, which inhibits the interaction between UHRF1 and histone H3. Our work identifies a mechanistic link between protein arginine methylation and DNA methylation, which is disrupted in cancer.
Source: Cell Reports
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Cancer Research Institute, Cancer Prevention and Research Institute of Texas, National Institutes of Health, University of Texas MD Anderson Cancer Center, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G132965223, G1727840030, The Future of Cancer Research: Training Program for Basic and Translational Scientists, Recruitment of Rising Stars, Mechanisms Regulating DNA Methylation Maintenance in Chromatin, The University of Texas MD Anderson Science Park Next-Generation Sequencing Facility, The Functional Analysis of the Coactivator CARM1, Factors that regulate chromatin organization and gene transcription, The Functional Analysis of the Coactivator CARM1, Molecular mechanisms of chromatin and epigenetic regulation, G6665716793, Modeling ICF syndrome in mice: Role of Zbtb24 in DNA methylation and antibody production, G8342724239, G9000346000, Cancer Center Support Grant
OpenAlex ID: W2776862258